The association between sleep and cognitive abnormalities in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is associated with attentional and processing abnormalities. Such abnormalities are also seen in healthy subjects with sleep disruption. We hypothesised cognitive abnormalities in BD patients would be worse in those with objectively verified sleep abnormalities. METHODS: Forty-six BD patients and 42 controls had comprehensive sleep/circadian rhythm assessment over 21 days alongside mood questionnaires. Cognitive function was assessed with a range of tasks including Psychomotor Vigilance Test (PVT), Attention Network Task (ANT) and Digit Symbol Substitution Test (DSST). BD participants with normal and abnormal sleep were compared with age- and sex-matched controls. RESULTS: BD patients had longer response times and made more lapses (responses >500 ms) than controls on the PVT (both p < 0.001). However, patients with normal sleep patterns did not differ from controls while those with sleep abnormalities did (p < 0.001). An identical pattern of effects were seen with the ANT response times, with the abnormality in bipolar abnormal sleepers related to the executive attentional network. Similarly, patients made fewer correct responses on the DSST compared with the controls (p < 0.001). Bipolar normal sleepers did not differ while those with abnormal sleep did (p < 0.001). All these differences were seen in bipolar abnormal sleepers who were euthymic (p < 0.01) and across the main abnormal sleep phenotypes. CONCLUSIONS: We confirm impairment in attention and processing speed in BD. Rather than sleep abnormalities exacerbating such dysfunction, the impairments were confined to bipolar abnormal sleepers, consistent with sleep disturbance being the main driver of cognitive dysfunction.

Does Cellular Metabolism from Primary Fibroblasts and Oxidative Stress in Blood Differ between Mammals and Birds? The (Lack-thereof) Scaling of Oxidative Stress.

As part of mitonuclear communication, retrograde and anterograde signaling helps maintain homeostasis under basal conditions. Basal conditions, however, vary across phylogeny. At the cell-level, some mitonuclear retrograde responses can be quantified by measuring the constitutive components of oxidative stress, the balance between reactive oxygen species (ROS) and antioxidants. ROS are metabolic by-products produced by the mitochondria that can damage macromolecules by structurally altering proteins and inducing mutations in DNA, among other processes. To combat accumulating damage, organisms have evolved endogenous antioxidants and can consume exogenous antioxidants to sequester ROS before they cause cellular damage. ROS are also considered to be regulated through a retrograde signaling cascade from the mitochondria to the nucleus. These cellular pathways may have implications at the whole-animal level as well. For example, birds have higher basal metabolic rates, higher blood glucose concentration, and longer lifespans than similar sized mammals, however, the literature is divergent on whether oxidative stress is higher in birds compared with mammals. Herein, we collected literature values for whole-animal metabolism of birds and mammals. Then, we collected cellular metabolic rate data from primary fibroblast cells isolated from birds and mammals and we collected blood from a phylogenetically diverse group of birds and mammals housed at zoos and measured several parameters of oxidative stress. Additionally, we reviewed the literature on basal-level oxidative stress parameters between mammals and birds. We found that mass-specific metabolic rates were higher in birds compared with mammals. Our laboratory results suggest that cellular basal metabolism, total antioxidant capacity, circulating lipid damage, and catalase activity were significantly lower in birds compared with mammals. We found no body-size correlation on cellular metabolism or oxidative stress. We also found that most oxidative stress parameters significantly correlate with increasing age in mammals, but not in birds; and that correlations with reported maximum lifespans show different results compared with correlations with known aged birds. Our literature review revealed that basal levels of oxidative stress measurements for birds were rare, which made it difficult to draw conclusions.

Estimating sleep parameters using an accelerometer without sleep diary.

Wrist worn raw-data accelerometers are used increasingly in large-scale population research. We examined whether sleep parameters can be estimated from these data in the absence of sleep diaries. Our heuristic algorithm uses the variance in estimated z-axis angle and makes basic assumptions about sleep interruptions. Detected sleep period time window (SPT-window) was compared against sleep diary in 3752 participants (range = 60-82 years) and polysomnography in sleep clinic patients (N = 28) and in healthy good sleepers (N = 22). The SPT-window derived from the algorithm was 10.9 and 2.9 minutes longer compared with sleep diary in men and women, respectively. Mean C-statistic to detect the SPT-window compared to polysomnography was 0.86 and 0.83 in clinic-based and healthy sleepers, respectively. We demonstrated the accuracy of our algorithm to detect the SPT-window. The value of this algorithm lies in studies such as UK Biobank where a sleep diary was not used.

Does efavirenz replacement improve neurological function in treated HIV infection?

OBJECTIVES: The contribution of specific antiretroviral drugs to cognitive function in HIV-infected people remains poorly understood. Efavirenz (EFV) may plausibly cause cognitive impairment. The objective of this study was therefore to determine whether chronic EFV therapy is a modifier of neurocognitive and neurometabolic function in the setting of suppressive highly active antiretroviral therapy. METHODS: We performed an open-label phase IV controlled trial. Adult subjects who were stable on suppressive EFV therapy for at least 6 months were switched to ritonavir-boosted lopinavir (LPV/r) with no change in the nucleoside reverse transcriptase inhibitor (NRTI) backbone. The following parameters were assessed before and 10 weeks after therapy switch: cognitive function (by CogState® computerized battery); brain metabolites (by proton magnetic resonance spectroscopy); brain activity [by attentional processing task-based functional magnetic resonance imaging]; and sleep quantity and quality [by sleep diary, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale]. RESULTS: Sixteen subjects completed the study. Despite most subjects (81%) self-reporting memory problems at baseline, cognitive function, brain metabolites, and brain activity showed no change at 10 weeks after switch. Sleep quality improved on switch off EFV [mean PSQI (standard deviation): EFV, 8.5 (6.5); LPV/r, 5.8 (5.5); mean difference -0.4; 95% confidence interval -6.0 to -0.7]. CONCLUSIONS: This is the first study to assess the effects of chronic EFV therapy on neurological function in a controlled setting. We conclude that EFV withdrawal is unlikely to result in significant modification of neurocognitive function in otherwise stable HIV-infected people.

Sleep and circadian rhythm disturbance in bipolar disorder.

BACKGROUND: Subjective reports of insomnia and hypersomnia are common in bipolar disorder (BD). It is unclear to what extent these relate to underlying circadian rhythm disturbance (CRD). In this study we aimed to objectively assess sleep and circadian rhythm in a cohort of patients with BD compared to matched controls. METHOD: Forty-six patients with BD and 42 controls had comprehensive sleep/circadian rhythm assessment with respiratory sleep studies, prolonged accelerometry over 3 weeks, sleep questionnaires and diaries, melatonin levels, alongside mood, psychosocial functioning and quality of life (QoL) questionnaires. RESULTS: Twenty-three (50%) patients with BD had abnormal sleep, of whom 12 (52%) had CRD and 29% had obstructive sleep apnoea. Patients with abnormal sleep had lower 24-h melatonin secretion compared to controls and patients with normal sleep. Abnormal sleep/CRD in BD was associated with impaired functioning and worse QoL. CONCLUSIONS: BD is associated with high rates of abnormal sleep and CRD. The association between these disorders, mood and functioning, and the direction of causality, warrants further investigation.

Twins conceived using IVF: a follow-up of the family environment and psychosocial adjustment in adolescence.

STUDY QUESTION: Compared to families with IVF singletons, what are parental depressive, parent-adolescent interaction and adolescent adjustment outcomes in families with 11-17-year-old IVF twins? SUMMARY ANSWER: No differences were detected for any measured outcome between families with 11-17-year-old IVF twins and those with IVF singletons, despite high statistical power. WHAT IS KNOWN ALREADY: When IVF twins are younger than 5-years-old, parents tend to have more mental health difficulties and poorer parent-child interactions relative to IVF singletons. By middle childhood, these differences may no longer exist and available studies with middle childhood-aged IVF twins challenge the expected long-term implications of the early concerns. IVF twins may even have more optimum adjustment than IVF singletons in middle childhood. STUDY DESIGN, SIZE, DURATION: Study of 280, 11-17-year-old IVF children (n = 122 twins and n = 158 singletons) from 195 families at a US reproductive endocrinology clinic. PARTICIPANTS/MATERIALS, SETTING, METHOD: At Wave 1, clinic patients with an IVF child born between 1998 and 2004 were invited to participate in an online survey. In this follow-up study, mothers and fathers provided information on each of their 11-17-year-old IVF adolescents. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences between 11- and 17-year-old IVF twins and IVF singletons in parent depressive symptoms, parent-adolescent interactions or adolescent adjustment outcomes. LIMITATIONS REASONS FOR CAUTION: Although the family demographics are representative of IVF patients, participants were drawn from one US clinic. WIDER IMPLICATIONS OF THE FINDINGS: Study results provide reassurance that by adolescence IVF twins and their families function as well as IVF singletons and their families. STUDY FUNDING/COMPETING INTERESTS: University of Minnesota (UMN) Agriculture Experiment Station (MN-52-107), UMN Grant-in-Aid of Research, Artistry and Scholarship, UMN College of Education and Human Development Research Development Investment Grant, UMN Women's Philosophic Leadership Circle Award, UMN Eva Miller Endowed Fellowship. The authors have no conflicts of interest to declare.

An update in sleep neurology: the latest bedtime stories.

In the 24/7 modern society, sleep disorders and the role of normal amounts and timing of sleep for health are often neglected by both doctors and their patients. Sleep has been said to be "of the brain, by the brain and for the brain" and the most immediate and obvious consequence of disrupted sleep is impaired brain function. This review will cover some of the recent papers published in both the Journal of Neurology and elsewhere in 2013/2014 that have advanced our knowledge of sleep and circadian rhythm disorders.

An unusual presentation of congenital central hypoventilation syndrome (Ondine's Curse).

Congenital central hypoventilation syndrome is a rare illness, which classically presents in the neonatal period; newborns present with shallow breathing and cyanosis, without a physiological rise in breathing rate. Incidence has been estimated from 1 in 10,000 to 1 in 200,000 live births. This case report describes the case of a young man who was asymptomatic until his presentation in acute respiratory failure at the age of 36 years. This case is reported to highlight the importance of considering this treatable illness as a potential cause of collapse and respiratory failure in adults presenting to emergency departments.

Cerebrospinal fluid hypocretin levels are normal in idiopathic REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a common sleep disorder that can be associated with a number of neurodegenerative conditions as well as with narcolepsy. Current diagnostic criteria require overnight polysomnography, and there are no other biomarkers available. The control of REM sleep is complex with a putative on/off switch within the brainstem activated, amongst other things, by hypocretinergic pathways from the lateral hypothalamus. METHODS: Cerebrospinal fluid hypocretin levels were measured in five patients with idiopathic RBD. RESULTS: Hypocretin levels were between 254 and 450 pg/ml and therefore within the normal range of >100 pg/ml. CONCLUSION: Hypocretin levels in patients with idiopathic RBD are normal.

Disrupted sleep and circadian patterns in frontotemporal dementia.

BACKGROUND: A study of the pattern of Sleep/Wake disturbance in frontotemporal dementia (FTD). METHODS: Sleep diaries and prolonged actigraphy were used to record the activity, sleep and wake of 13 patients with a clinical diagnosis of FTD. These were compared with diaries and actigraphy from normal age/sex matched controls and also to a population with probable Alzheimer's disease (AD). RESULTS: There was significant sleep/wake disturbance in FTD. This occurred throughout the course of the illness and the nature of the sleep disturbance was different to patients with AD. FTD subjects showed increased nocturnal activity and decreased morning activity compared with controls, suggesting possible phase delay. Sleep diary data confirmed decreased sleep efficiency and decreased total sleep in all FTD patients. CONCLUSIONS: We describe significant sleep disturbance in non-institutionalized patients with FTD and suggest that early sleep disturbance may help differentiate between FTD and AD.

A model immunization demonstration for preschoolers in an inner-city barrio, San Diego, California, 1992-1994.

An immunization demonstration project was conducted in an inner-city Latino neighborhood in San Diego to address underimmunization of children of preschool age. The project attempted interventions on consumer, provider, and system levels to reduce barriers to immunization and raise immunization rates. Free walk-in immunization clinics with emphasis on cultural sensitivity and that incorporated computerized reminder/recall were established. An educational series was offered to community health center (CHC) providers, and extensive community-based outreach and education took place in schools, churches, a WIC site, etc. Evaluation activities included preintervention and postintervention provider knowledge, attitudes, and practice surveys, CHC chart audits, and household surveys in the intervention ZIP code area and a control ZIP code area. Immunization coverage for 4DPT, 3OPV, and 1MMR (4:3:1) among two-year-olds increased significantly from 37% to 50% overall, and to 59% in the 1991 birth cohort in the intervention area compared to a one percentage point overall increase in the control area. Coverage improved significantly and missed opportunities decreased in one intervention CHC that participated most actively in educational inservices. While the Year 2000 U.S. Public Health Service objective of 90% 4:3:1 coverage for two-year-olds was not achieved over the 21-month course of the project, the results approached the 1996 single-antigen objectives. This demonstration underscores the importance of multilevel interventions including low cost, no appointment, and culturally appropriate immunization services for the indigent; the use of computerized reminder systems; and provider assessment, education, and feedback in the effort to raise preschool immunization levels. Medical Subject Headings (MeSH): immunization, preschool-age children, health promotion, provider education, immunization monitoring and follow-up systems, pediatric immunization standards, household surveys.

Physical similarity and young children's understanding of scale models.

Young children's understanding of the correspondence between a scale model and a larger space is affected by the degree of physical similarity between the 2 spaces. In 4 studies, children between 2.5 and 3.5 years of age watched as a miniature toy was hidden somewhere in a scale model of a room. They were then asked to find an analogous toy that was hidden in the corresponding place in the room itself. The effects of different levels of 3 types of physical similarity were investigated. In general, the children's retrieval scores increased as a function of increasing similarity, although younger children required a higher degree of similarity to appreciate the model-room correspondence than did older children. Some types of similarity were more important than others: The level of similarity between the objects within the 2 spaces and of the overall size of the spaces both had large effects on the children's performance. Similarity presumably affects accessibility, the likelihood that children's representation of one space will provide access to their representation of the other space.